Effects of progestogen neurosteroids on locomotor activity in zebrafish embryos and larvae.

IF 2.5 3区 农林科学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Mandarin Mathouchanh, Charles A Lessman
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Abstract

The steroid hormone progesterone (P4) and related compounds called progestogens are well known for their effects on the reproductive system. However, their physiological roles outside reproduction are less understood. Additionally, there is limited information on the toxicological repercussions of environmental exposure to exogenous progestogens and how such exposure might impact the development and survival of animals living in contaminated habitats. Two progesterone-based neurosteroids, allopregnanolone and tetrahydrodeoxycorticosterone (THDOC), are known to enhance γ-aminobutyric acid type A (GABAA) receptor activity, inducing neuronal hyperpolarization. In this study, locomotor parameters in zebrafish embryos and larvae were used as endpoints to assess the inhibitory effects of pregnane neurosteroids. Specifically, spontaneous tail coiling in embryos at 24 h post-fertilization (hpf) and swimming activity in larvae aged 120-168 hpf were evaluated. Motility assays in embryos showed that P4 increased spontaneous tail coiling, whereas larvae exhibited an anesthetic-like loss of motility. This effect was both age- and dose-dependent for P4, deoxycorticosterone (DOC), 5α-dihydroprogesterone, and the membrane progesterone receptor agonist, ORG-OD-02-0, but not for other steroids tested. Removal of the steroids after the onset of anesthesia led to recovery of motility in larvae, suggesting that the observed effects are not due to a non-specific toxicity. Our results suggest that P4 targets the mPR, which acts in association with the GABAA receptor to mediate the loss of locomotor behavior. This study provides further insight into how neuroactive compounds can affect locomotor behaviors during early developmental stages in nonmammalian species.

孕激素神经类固醇对斑马鱼胚胎和幼虫运动活性的影响。
众所周知,类固醇激素黄体酮(P4)和相关化合物孕激素对生殖系统的影响。然而,它们在生殖之外的生理作用却鲜为人知。此外,关于环境暴露于外源性孕激素的毒理学影响以及这种暴露如何影响生活在受污染栖息地的动物的发育和生存的信息有限。两种以孕激素为基础的神经甾体,异孕酮和四氢脱氧皮质酮(THDOC),已知可增强γ-氨基丁酸A型(GABAA)受体活性,诱导神经元超极化。本研究以斑马鱼胚胎和幼虫的运动参数为终点,评估妊娠期神经类固醇的抑制作用。具体来说,研究了受精后24 h胚胎的自发尾卷和120 ~ 168 hpf幼虫的游泳活动。胚胎的运动性实验表明,P4增加了自发的尾巴卷曲,而幼虫表现出类似麻醉剂的运动性丧失。对于P4、去氧皮质酮(DOC)、5α-二氢孕酮和膜孕酮受体激动剂ORG-OD-02-0,这种影响是年龄和剂量依赖的,但对其他类固醇没有影响。在麻醉开始后去除类固醇导致幼虫运动能力恢复,这表明观察到的效果不是由于非特异性毒性。我们的研究结果表明P4靶向mPR, mPR与GABAA受体一起介导运动行为的丧失。这项研究为神经活性化合物如何影响非哺乳动物早期发育阶段的运动行为提供了进一步的见解。
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来源期刊
Fish Physiology and Biochemistry
Fish Physiology and Biochemistry 农林科学-生化与分子生物学
CiteScore
5.60
自引率
6.90%
发文量
106
审稿时长
4 months
期刊介绍: Fish Physiology and Biochemistry is an international journal publishing original research papers in all aspects of the physiology and biochemistry of fishes. Coverage includes experimental work in such topics as biochemistry of organisms, organs, tissues and cells; structure of organs, tissues, cells and organelles related to their function; nutritional, osmotic, ionic, respiratory and excretory homeostasis; nerve and muscle physiology; endocrinology; reproductive physiology; energetics; biochemical and physiological effects of toxicants; molecular biology and biotechnology and more.
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